Journal
JOURNAL OF PHYSICAL CHEMISTRY B
Volume 114, Issue 39, Pages 12632-12640Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jp1001786
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Funding
- National Heart, Lung and Blood Institute [U01 HL080718]
- National Cancer Institute [U54 CA 119335]
- National Science Foundation [DMR05-20415]
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This work investigated the stability of DSPE-PEG(2000) micelles in the presence of bovine serum albumin (BSA). DSPE-PEG(2000) was found to exist in equilibrium among monomeric, micellar, and BSA-bound states, and this equilibrium shifted toward the BSA-bound state when the temperature increased from 20 to 37 degrees C. The micellar state is thermodynamically unstable at both temperatures when the concentration of BSA approaches that of DSPE-PEG(2000), and micelle breakup occurs with a first-order time constant of 130 +/- 9 min at 20 degrees C and 7.8 +/- 1.6 min at 37 degrees C. Thus, previous targeting experiments that demonstrate synergistic effects in multiply functionalized DSPE-PEG(2000) micelles are likely due to targeting that occurs on a timescale faster than that of micelle breakup. Micelle breakup was limited by diffusion at 20 degrees C whereas at 37 degrees C monomer desorption from the micelle was the rate-limiting step. These findings give clear guidance concerning the lifetimes of micelles that may be used as diagnostic and therapeutic nanoparticles.
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